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Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer

Lookup NU author(s): Dr Max RobinsonORCiD

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Abstract

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 x 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 x 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 x 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers.


Publication metadata

Author(s): Lesseur C, Diergaarde B, Olshan AF, Wunsch V, Ness AR, Liu G, Lacko M, Eluf-Neto J, Franceschi S, Lagiou P, Macfarlane GJ, Richiardi L, Boccia S, Polesel J, Kjaerheim K, Zaridze D, Johanson M, Menezes AM, Curado MP, Robinson M, Ahrens W, Canova C, Znaor A, Castellsague X, Conway DI, Holcatova I, Mates D, Vidensky M, Healy CM, Szeszenia-Dbrowska N, Fabianova E, Lissowska J, Grandis JR, Weissler MC, Tajara EH, Nunes FD, de Carvalho MB, Thomas S, Hung RJ, Peters WHM, Herrero R, Cadoni G, Bueno-De-Mesquita HB, Steffen A, Agudo A, Shangina O, Xiao XJ, Gaborieau V, Chabrier A, Anantharaman D, Boffetta P, Amos CI, Mckay JD, Brennan P

Publication type: Article

Publication status: Published

Journal: Nature Genetics

Year: 2016

Volume: 48

Issue: 12

Pages: 1544-1550

Print publication date: 01/12/2016

Online publication date: 17/10/2016

Acceptance date: 01/09/2016

ISSN (print): 1061-4036

ISSN (electronic): 1546-1718

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ng.3685

DOI: 10.1038/ng.3685


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Funding

Funder referenceFunder name
Compagnia di San Paolo/FIRMS
National Cancer Institute of Canada
Pan-American Health Organization
Region Piemonte
UICC Yamagiwa-Yoshida Memorial International Cancer Study
Associazione Italians per la Ricerca sul Cancro
Cancer Care Ontario Research Chair
European Commission (DG SANCO)
Fondazione Veronesi
Fondo para la Investigacion Cientifica y Tecnologica (Argentina)
International Agency for Research on Cancer
Italian Association for Cancer Research
01/01768-2Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
020214Canadian Cancer Society Research Institute
04/12054-9Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
1X01HG007780-0US National Institute of Dental and Craniofacial Research (NIDCR)
10/51168-0Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
BAE 01/5013Fondo de Investigaciones Sanitarias, Spain
CA92039US NIH/National Cancer Institute
CPDA057222Padova University
FIS 97/0024Fondo de Investigaciones Sanitarias, Spain
FIS 97/0662Fondo de Investigaciones Sanitarias, Spain
IC15-CT98-0332European Commission's INCO-COPERNICUS Program
IG 2011 10491Associazione Italiana per la Ricerca sul Cancro (AIRC)
IG 2013 14220Associazione Italiana per la Ricerca sul Cancro (AIRC)
IC18-CT97-0222European Commission INCO-DC programme
P30CA047904US National Institutes of Health
P50CA097190US National Institutes of Health
QLK1-2001-00182European Commission's fifth framework programme
R01CA90731National Cancer Institute
U19CA148127National Cancer Institute
RP-PG-0707-10034National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme
S06 96 202489 05F02Europe against Cancer
WCRF 99A28World Cancer Research Foundation
X01HG007492-0

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